EP0336147A2 - Monoesters du diéthylène glycol, leur procédé de préparation et leur utilisation comme médicaments - Google Patents
Monoesters du diéthylène glycol, leur procédé de préparation et leur utilisation comme médicaments Download PDFInfo
- Publication number
- EP0336147A2 EP0336147A2 EP89104496A EP89104496A EP0336147A2 EP 0336147 A2 EP0336147 A2 EP 0336147A2 EP 89104496 A EP89104496 A EP 89104496A EP 89104496 A EP89104496 A EP 89104496A EP 0336147 A2 EP0336147 A2 EP 0336147A2
- Authority
- EP
- European Patent Office
- Prior art keywords
- diethylene glycol
- lonazolac
- acid
- water
- glycol monoester
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/415—1,2-Diazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/196—Carboxylic acids, e.g. valproic acid having an amino group the amino group being directly attached to a ring, e.g. anthranilic acid, mefenamic acid, diclofenac, chlorambucil
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C229/40—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino groups bound to carbon atoms of at least one six-membered aromatic ring and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton
- C07C229/42—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino groups bound to carbon atoms of at least one six-membered aromatic ring and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton with carboxyl groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by saturated carbon chains
Definitions
- the esterification of the acids (a) to (e) can also be carried out under acidic catalysis without removing the water of reaction at medium temperatures and short reaction times, if 8 to 15 mol of diethylene glycol, preferably 10.5 to 12, per mole of acid Mol can be used.
- Suitable acidic catalysts are Lewis acids, zinc chloride, sulfuric acid, phosphoric acid, polyphosphoric acid, benzenesulfonic acid, p-toluenesulfonic acid or mixtures of phosphoric acid and p-toluenesulfonic acid, in molar ratios of 0.1 to 1.0 mol of catalyst per mol of acid.
- the reaction temperature is 60 * to 120 °, preferably 80 to 100 'with reaction times of 1 to 5 hours.
- reaction water remaining in the batch allows such a high ester yield, since, according to the current teaching, on which DE-PS 28 34 167 is based, the reaction equilibrium is shifted in favor of the ester, and the water of reaction is removed. azeotropic orbiting is required.
- the excess of diethylene glycol after neutralization with alkali or alkaline earth metal hydroxides or carbonates optionally added in solid form is removed by distillation or advantageously by adding water, the crude ester separating out or being obtained by extraction with suitable solvents.
- the crude ester obtained is either distilled in a two-stage vacuum short-path distillation system or purified by means of preparative medium-pressure liquid chromatography over conventional sorbents, preferably silica gel. Pressures of 10-20 bar are suitable.
- the diethylene glycol monoesters according to the invention have anti-inflammatory properties. They can be used in medicinal products, whereby the concentration and dosage correspond to those of the known basic acid bodies.
- the anti-inflammatory properties of the new esters were measured in comparison to the respective standard in the rat's paw edema test.
- the inhibitory effect relates to the respective value of the untreated control group to which the vehicle was administered. The results are summarized in Table 1.
- the new esters are effectively superior to the respective acid as a standard.
- the same inhibitory effect is achieved after oral administration with a significantly reduced dose of the esters or is more pronounced (Lonazolac).
- the esters with equimolar dosing are clearly superior within the measurement period.
- esters according to the invention are used in pharmaceuticals for dermal use in concentrations of 1 to 20% by weight, preferably 5 to 10% by weight.
- Suitable dermal formulations are ointments and creams of the oil-in-water (O / W) or water-in-oil (W / O) type using conventional salve bases and auxiliaries, such as fat components, emulsifiers and stabilizers, and also gels using Tylose, Carboxymethyl cellulose, salts of acrylic acid polymers or acrylic acid-acrylamide copolymers as structuring agents in aqueous or alcoholic aqueous preparation forms, and solutions in dermally compatible solvents, such as alcohol, alcohol-water mix. or fatty alcohols and esters.
- dermal formulations which additionally contain penetration mediators, such as dimethyl sulfoxide in concentrations of 10 to 40% by weight or urea with 5 to 10% by weight.
- penetration mediators such as dimethyl sulfoxide in concentrations of 10 to 40% by weight or urea with 5 to 10% by weight.
- the pharmaceuticals thus produced are used to combat diseases of the rheumatic type.
- the diethylene glycol monoesters from Lonazolac and Diciofenac are particularly preferred.
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Rheumatology (AREA)
- Pain & Pain Management (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE3811118A DE3811118C1 (fr) | 1988-03-31 | 1988-03-31 | |
DE3811118 | 1988-03-31 |
Publications (2)
Publication Number | Publication Date |
---|---|
EP0336147A2 true EP0336147A2 (fr) | 1989-10-11 |
EP0336147A3 EP0336147A3 (fr) | 1991-03-20 |
Family
ID=6351239
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP19890104496 Withdrawn EP0336147A3 (fr) | 1988-03-31 | 1989-03-14 | Monoesters du diéthylène glycol, leur procédé de préparation et leur utilisation comme médicaments |
Country Status (6)
Country | Link |
---|---|
US (1) | US4960793A (fr) |
EP (1) | EP0336147A3 (fr) |
JP (1) | JPH026432A (fr) |
KR (1) | KR890014105A (fr) |
DE (1) | DE3811118C1 (fr) |
FI (1) | FI891409A (fr) |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2009037705A2 (fr) * | 2007-09-20 | 2009-03-26 | Ramot At Tel Aviv University Ltd. | Méthodes et compositions utiles pour le traitement du cancer et de l'inflammation |
US8278357B2 (en) | 2002-10-21 | 2012-10-02 | Ramot At Tel-Aviv University Ltd. | Derivatives of N-phenylanthranilic acid and 2-benzimidazolone as potassium channel and/or neuron activity modulators |
US8765815B2 (en) | 2007-09-20 | 2014-07-01 | Ramot At Tel-Aviv University Ltd. | N-phenyl anthranilic acid derivatives and uses thereof |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA2498943A1 (fr) * | 2002-09-20 | 2004-04-01 | Nicox S.A. | Procede de fabrication de composes donneurs de no tels que du diclofenac donneur de no |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE2658610A1 (de) * | 1975-12-24 | 1977-07-07 | Hisamitsu Pharmaceutical Co | Phenylessigsaeureesterderivate |
DE3636125A1 (de) * | 1985-10-25 | 1987-04-30 | Espanola Prod Quimicos | Verfahren zur herstellung von diethylenglykolestern |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB728642A (en) * | 1950-02-15 | 1955-04-20 | Ciba Ltd | Polyglycol esters of homocyclic organic carboxylic acids and a process of making thesame |
DE2834168C2 (de) * | 1978-08-04 | 1984-02-09 | Troponwerke GmbH & Co KG, 5000 Köln | Verfahren zur Herstellung von 2-(2-Hydroxyäthoxy)äthyl-N-(α,α,α-trifluor-m-tolyl)anthranilat |
DE2834167C2 (de) * | 1978-08-04 | 1984-01-26 | Troponwerke GmbH & Co KG, 5000 Köln | Verfahren zur Herstellung von 2-(2-Hydroxyäthoxy)äthyl-N-(α,α,α-trifluor-m-tolyl)anthranilat |
CA1201127A (fr) * | 1982-09-10 | 1986-02-25 | Katsuhiro Uchida | Derive d'acide biphenylpropionique; methode de preparation et composition pharmaceutique qui en renferme |
-
1988
- 1988-03-31 DE DE3811118A patent/DE3811118C1/de not_active Expired
-
1989
- 1989-03-14 EP EP19890104496 patent/EP0336147A3/fr not_active Withdrawn
- 1989-03-23 FI FI891409A patent/FI891409A/fi not_active IP Right Cessation
- 1989-03-27 KR KR1019890003842A patent/KR890014105A/ko not_active Application Discontinuation
- 1989-03-30 JP JP1076844A patent/JPH026432A/ja active Pending
- 1989-03-31 US US07/331,124 patent/US4960793A/en not_active Expired - Fee Related
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE2658610A1 (de) * | 1975-12-24 | 1977-07-07 | Hisamitsu Pharmaceutical Co | Phenylessigsaeureesterderivate |
DE3636125A1 (de) * | 1985-10-25 | 1987-04-30 | Espanola Prod Quimicos | Verfahren zur herstellung von diethylenglykolestern |
Cited By (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US8278357B2 (en) | 2002-10-21 | 2012-10-02 | Ramot At Tel-Aviv University Ltd. | Derivatives of N-phenylanthranilic acid and 2-benzimidazolone as potassium channel and/or neuron activity modulators |
US8618169B2 (en) | 2002-10-21 | 2013-12-31 | Ramot At Tel-Aviv University Ltd. | Derivatives of N-phenylanthranilic acid and 2-benzimidazolone as potassium channel and/or neuron activity modulators |
WO2009037705A2 (fr) * | 2007-09-20 | 2009-03-26 | Ramot At Tel Aviv University Ltd. | Méthodes et compositions utiles pour le traitement du cancer et de l'inflammation |
WO2009037705A3 (fr) * | 2007-09-20 | 2009-07-09 | Univ Ramot | Méthodes et compositions utiles pour le traitement du cancer et de l'inflammation |
US8765815B2 (en) | 2007-09-20 | 2014-07-01 | Ramot At Tel-Aviv University Ltd. | N-phenyl anthranilic acid derivatives and uses thereof |
US9403756B2 (en) | 2007-09-20 | 2016-08-02 | Ramot At Tel-Aviv University Ltd. | N-phenyl anthranilic acid derivatives and uses thereof |
Also Published As
Publication number | Publication date |
---|---|
KR890014105A (ko) | 1989-10-21 |
US4960793A (en) | 1990-10-02 |
JPH026432A (ja) | 1990-01-10 |
DE3811118C1 (fr) | 1989-10-12 |
FI891409A0 (fi) | 1989-03-23 |
EP0336147A3 (fr) | 1991-03-20 |
FI891409A (fi) | 1989-10-01 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
DE3690187C2 (de) | Naphthalinderivate mit retinoider Wirkung, Verfahren zu deren Herstellung und diese enthaltende pharmazeutische und kosmetische Mittel | |
EP0857712A1 (fr) | Procédé pour la préparation d'acides malonique et alkylmaloniques | |
DE2349707A1 (de) | N-(mercaptoacyl)-aminosaeuren, verfahren zu deren herstellung und diese verbindungen enthaltende arzneimittel | |
DE2556474C2 (de) | Substituierte p-Benzyloxyphenylessigsäuren, ihre Herstellung sowie diese enthaltende Arzneimittel | |
EP0029247B1 (fr) | Acides alcényl-thiényl-alcane carboxyliques et leurs dérivés, procédé pour leur préparation et médicaments les contenant | |
EP0335164A2 (fr) | Dérivés esters du néopentanol, leur procédé de fabrication et leur utilisation comme médicaments | |
DE2228448A1 (de) | Stoffwechselwirksame derivate der bis(4-hydroxy-phenyl)-alkansaeure sowie verfahren zu ihrer herstellung | |
CH644263A5 (de) | Fuer kosmetische zwecke verwendbare praeparate und verfahren zur herstellung der wirkstoffe dieser praeparate. | |
DE2252637C3 (de) | Verwendung von 1,3-Glycerindiäthern | |
DE3811118C1 (fr) | ||
EP0133935A2 (fr) | Dérivés d'acides p-oxybenzoiques, procédés pour leur préparation et leur utilisation pour la préparation de médicaments ayant une activité hypolipémique | |
DE68915094T2 (de) | Benzofuranverbindungen, Verfahren zu ihrer Herstellung, diese enthaltende pharmazeutische und kosmetische Zusammenstellungen und Verwendung dieser Zusammenstellungen. | |
DE1932389B2 (de) | Neue 2-Naphthyl-2-methyläthanole und deren Acetate, sie enthaltende Arzneimittel und Verfahren zu ihrer Herstellung | |
DE2251556C3 (de) | Verfahren zu ihrer Herstellung und diese enthaltende Arzneimittel | |
DE2462967C2 (de) | Derivate des 3-Amino-5-methyl-2-phenyl-pyrrols, deren Salze und diese enthaltende pharmazeutische Zubereitung | |
DE2500808B2 (de) | 4-cyclopropylmethylenoxy-3-chlorphenylessigsaeure und ihre salze, verfahren zu deren herstellung sowie diese enthaltende arzneimittel | |
DE1493618A1 (de) | Cumarinderivate und ein Verfahren zu ihrer Herstellung | |
EP0031562B1 (fr) | Oxazolines, leur préparation et compositions pharmaceutiques les contenant | |
EP0498011B1 (fr) | Sels de l'acide 2-(2,6-dichloroanilino)-phénylacétique procédé pour leur préparation et leur application comme préparation pharmaceutique pour utilisation topique | |
EP0174624A1 (fr) | Procédé de préparation d'esters de l'acide lactique | |
DE3019834C2 (de) | Ester von 2-(4-Isobutylphenyl)-propanol-1, Verfahren zu ihrer Herstellung und diese Verbindungen enthaltende Arzneimittel | |
DE2534453C2 (de) | Phenoxyalkancarbonsäureester von Oxyalkylsalicylaten, Verfahren zu ihrer Herstellung und diese enthaltende Arzneimittel | |
DE2753768A1 (de) | Antiphologistisch wirkende arzneimittel | |
Siggins et al. | Myelographic Agents. I. Iodobenzoates | |
DE2223855C3 (de) | Derivate der Phenylessigsäure, deren therapeutisch verträgliche Niedrigalkylester und die Salze dieser Verbindungen, Verfahren zur Herstellung dieser Verbindungen und diese Verbindungen enthaltende Arzneimittel |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PUAI | Public reference made under article 153(3) epc to a published international application that has entered the european phase |
Free format text: ORIGINAL CODE: 0009012 |
|
AK | Designated contracting states |
Kind code of ref document: A2 Designated state(s): AT BE CH DE ES FR GB GR IT LI LU NL SE |
|
PUAL | Search report despatched |
Free format text: ORIGINAL CODE: 0009013 |
|
AK | Designated contracting states |
Kind code of ref document: A3 Designated state(s): AT BE CH DE ES FR GB GR IT LI LU NL SE |
|
17P | Request for examination filed |
Effective date: 19910828 |
|
STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN |
|
18D | Application deemed to be withdrawn |
Effective date: 19921001 |